Answers

Short answers

1 Dextrocardia, situs inversus, and patchy areas of bronchial wall thickening can be seen. The haziness in the right lower zone may indicate consolidation.

2 The diagnosis is primary ciliary dyskinesia.

3 Patients may present with sinusitis, bronchitis, pneumonia, and otitis media¹ or with a history of neonatal respiratory distress, dextrocardia with situs inversus,² or complex congenital heart diseases with situs ambiguus.³ Affected women may present with subfertility or ectopic pregnancy, owing to defective ciliary action in the fallopian tube; men may be infertile owing to diminished sperm motility.¹

4 Screening tests are measurement of nasal nitric oxide, which is consistently low in patients with primary ciliary dyskinesia,⁴ and the "saccharin test," which assesses mucociliary function.⁵ Diagnosis is made through ciliary biopsy. The sample is analysed under light microscopy, looking at the frequency and pattern of ciliary beats, and the ultrastructure is examined through electron microscopy.⁶

Long answers
1 Abnormalities
Figure 2 shows the abnormalities.

View larger version (28K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2 Abnormalities present on chest radiograph of 5 year old boy

 
2 Diagnosis
Primary ciliary dyskinesia is a genetic disorder of ciliary motility that is usually inherited by the autosomal recessive route. Each cilium is a ring of nine parallel microtubule doublets interlinked by inner and outer dynein arms and surrounded by an extension of the plasma membrane. Respiratory cilia have a pair of central microtubules; this makes up the classical 9+2 arrangement. Some patients with primary ciliary dyskinesia have central pair defects, where the central pair is either absent or transposed. Retinal cilia, renal cilia, and other cilia may have 9+0 as the usual arrangement.

Motile cilia move fluid across an epithelium and are present in the airways, the eustachian tube, ventricles of the brain, and the male and female reproductive tracts. Dysfunction of motile cilia causes impaired mucociliary clearance and retention of inhaled particles in the lung, paranasal sinuses, and middle ear. In the developing embryo, ciliary activity controls the movement of fluid that determines laterality. In patients with primary ciliary dyskinesia, organs can be on either side.

Ciliary dysfunction is implicated in a range of diseases known collectively as the ciliopathies: polycystic kidney disease and chronic tubulointerstitial nephritis, retinitis pigmentosa, sensorineural deafness and vestibular impairment, anosmia, hydrocephalus, and biliary atresia.⁷ All ciliopathies arise from defective cilia, but the range of symptoms varies because of the structural diversity of cilia.⁸

3 Other presentations
The estimated incidence of primary ciliary dyskinesia is 1 in 15 000 to 30 000 births. Symptoms are commonly present from birth or early infancy, but many patients will receive the diagnosis after a period of chronic ill health with recurrent lower respiratory tract infections, persistent serous otitis media, and possible hearing loss. Patients may report a history of neonatal respiratory distress requiring several days of treatment with oxygen; some have needed prolonged mechanical ventilation.² Clinical manifestations include chronic bronchitis, chronic sinusitis, chronic otitis media, and reduced fertility. Many patients experience hearing loss, and some may also describe a poor sense of smell due to high mucus production in the sinuses. About half of patients with primary ciliary dyskinesia have Kartagener’s triad of situs inversus totalis, bronchiectasis, and rhinosinusitis,⁶ and 6% may present with complex congenital heart diseases with situs ambiguus.³

4 Screening and diagnostic tests
Screening tests for primary ciliary dyskinesia have their limitations. The saccharin test is designed to assess mucociliary function but is unreliable in children (and is not used in paediatric patients in the United Kingdom). The most sensitive and specific screening test is measurement of nasal nitric oxide, which is very low in patients with primary ciliary dyskinesia. This test is available only in specialist centres, however, and may be difficult to use in young children.⁴

Failure to diagnose the condition leads to progressive and permanent lung destruction and to inappropriate ear, nose, and throat surgery. Primary ciliary dyskinesia should be suspected, along with other possible diagnoses such as cystic fibrosis and immunological defects, in children who have a persistent "wet" sounding or productive cough.¹

A chest x ray may be normal or show dextrocardia (in about half of patients) and therefore raise clinical suspicion. Other common x ray findings are hyperinflation and bronchial wall thickening.⁹ High resolution computed tomography may identify severity and distribution of the disease but is not diagnostic. In primary ciliary dyskinesia the middle and lower lobes are more commonly affected, as opposed to the upper lobes or a more diffuse pattern in cystic fibrosis. ¹⁰ Echocardiography may show complex congenital heart diseases.

Diagnosis can be confirmed from ciliary biopsy. This provides measurements of ciliary beat frequency, high speed analysis of ciliary beat pattern, detailed electron microscopy of ciliary ultrastructure, and, in some specialist centres, cell culture from biopsies. Primary cell culture, where successful, will confirm or exclude the diagnosis with 100% certainty.

Management
No specific treatments will correct ciliary dysfunction, and management is aimed at preventing deterioration in lung function. Where possible, patients should be cared for in a specialist respiratory unit, with joint care from otorhinolaryngology and audiology specialists with experience in this condition.

Patients should have regular respiratory monitoring, including pulmonary function tests, regular culturing of sputum and cough swabs, and, where appropriate, high resolution computed tomography to assess the extent of bronchiectasis. They should have regular airway clearance through physiotherapy and are encouraged to exercise regularly. Respiratory tract infections need to be treated aggressively with appropriate antibiotics. We found no good evidence to support the use of prophylactic antibiotics, mucolytics, or bronchodilators.¹

Although management of primary ciliary dyskinesia is similar to cystic fibrosis, the prognosis is not. Patients with primary ciliary dyskinesia can have a normal or near normal lifespan if they are diagnosed and treated early to prevent the progression of lung disease. We found no data on the lifespan of patients with primary ciliary dyskinesia. In general, the condition is associated with a better prognosis than is cystic fibrosis. The disease has a wide spectrum of severity; some patients with severe bronchiectasis need lung transplantation in early adulthood.

Cite this as: BMJ 2009;338:b945